It has long been known that certain naturally biologically active substances can be obtained from the glands of animals and the substances so obtained utilized in the treatment of deficiencies of the human body. One such substance is adrenocorticotropic hormone, commonly called ACTH, which may be obtained from the pituitary glands of animals.
The burden of having to collect the relatively small pituitary glands of animals, and the tedious processes involved in their extraction to obtain only a small amount of active material, made it desirable to discover practical methods for synthesizing the biologically active substances.
We are aware of disclosures of certain laboratory methods for the synthesis of certain peptides of relatively short amino acid chain lengths. These include an article by R. B. Merrifield entitled "Solid Phase Peptide Synthesis I. The Synthesis of a Tetrapeptide" at pages 2149 to 2154 in Vol. 85 of Journal of the American Chemical Society (1963) and a book entitled "Solid Phase Peptide Synthesis" by John W. Stewart and Janis D. Young published by W. H. Freemand and Company of San Francisco, California.
In our U.S. Pat. No. 3,915,949 dated Oct. 28, 1975 we set forth practical methods by which the hormone ACTH may be synthesized. This substance includes a chain of 39 amino acid residues in a certain prescribed sequence. In this synthesis of the biological substance each of the amino acid moieties have to be added to a molecular structure one at a time and in a certain sequence, and each of such reactions contribute to the chance for errors which may accumulate to ruin the product or seriously affect its efficacy.
Accordingly, we have attempted to synthesize new substances having shorter amino acid chain lengths which are as active biologically or which may be even more active than substances previously known, and have sought ways for preparing such substances. Further, we have sought new methods and new intermediates which facilitate the preparation of the new biologically active substances.